The mouse mammary tumor virus (MMTV) is a retrovirus which has been shown to act as an insertional mutagen that causes the deregulation of expression of cellular genes adjacent to the site of MMTV integration in mammary tumors (Varmus, H. E. (1982). Cancer Surv., 1:309-320). Mice infected with MMTV frequently develop preneoplastic hyperplastic alveolar nodules (HAN) (Daniel, C., et al. Proc. Natl. Acad. Sci. USA., 61:53-60; DeOme, K. B., (1959) J. Natl. Cancer Inst., 78:751-757; Medina, D., (1973) Methods Cancer Res., 7:3-53; Smith, G., et al. (1984) Cancer Res., 44:3426-3437) and the passage of these nodules in cleared mammary fat pads of syngeneic mice by serial outgrowth often results in the development of mammary tumors within these mice in a stochastic manner. In addition, it is not uncommon to find metastatic lesions in the lungs of mice bearing outgrowths with mammary tumors. For these reasons, there is considerable interest in identifying MMTV-induced mutational events that may contribute to different stages of tumor development.
Using the MMTV genome as a molecular tag, five loci (Wnt-1/Int-1, Fgf-3/Int-2, Int-3, Wnt-3, and Fgf-4/Hst/k-FGF) have been identified which represent common integration sites (designated Int loci) for MMTV in mouse mammary tumors (Dickson, C., et al. (1984) Cell., 37:529-536; Gallahan, D., et al. (1987) J. Virol., 61:218-220; Nusse,.R., et al. (1982) Cell., 31:99-109; Peters, G., et al. (1989) Proc. Natl. Acad. Sci. USA., 86:5678-5682). Transgenic mouse studies utilizing transgenes in which the MMTV LTR was linked to either the WNT-1, Fgf-3, or Int-3 genes have demonstrated that activation of expression of these genes contributes to mammary tumorigenesis (Jhappan, C., et al. (1992) Genes & Develop., 6:345-355; Muller, W. J., et al. (1990) Embo J., 9:907-913; Tsukamoto, A. S., et al. (1988) Cell., 55:619-625).
The present invention describes the isolation of a new Int gene designated Int6 and the use of the gene, its gene product, and reagents derived from the gene and its gene product, in diagnostic methods, vaccines, immunotherapy and gene therapy.